Cholangiocarcinoma refers to any malignancy originating in the intra- or extrahepatic bile ducts. These tumors probably represent 10-15% of primary hepatobiliary cancers, and their incidence in the United States is estimated at up to 3,000 per year. See Yeo et al. Surg. Clin. North Amer. 70:1429 (1990); Vogt et al. Oncology 2:37 (1988). The prognosis for these tumors is universally dismal, with a majority of patients dying within six months to one year of diagnosis. See Imrie et al. Wright's Liver and Biliary Diseases, Vol 2, 3d ed., p. 1516 (1992).
Cholangiocarcinomas are notoriously difficult to diagnose. The diagnosis is usually performed by non-invasive imaging studies (e.g., ultrasound or CT scan) with an overall accuracy of only about 50%. Positive histology is required for absolute diagnosis, and this is most effectively performed by fine needle aspiration biopsy. Desa et al. Gut 32(10):1188 (1991); Bedrossian et al. Arch. Patho. Lab. Med. 113(11):1225 (1989). However, by the time this diagnosis is made, the disease has commonly reached the point where curative surgical therapy is impossible. Yeo et al. Cholangiocarcinoma (Review) Surg. Clin. North Amer. 70:1429 (1990); Miyazaki et al. Surg. Ther. 56:443 (1987).
Surgical resection presently provides the best hope for cure. Only ten percent of patients with cholangiocarcinomas, however, are surgically treatable because of the location of their tumors. See Nargoney et al., Sem. Oncol. 15:106 (1988). Even after resection, twenty-five percent of these patients will still have residual tumors, and the five year survival rate for resected patients is only thirteen percent with an operative mortality up to twelve percent. See Yeo et al., Surg. Clin. North Amer. 70:1429 (1990); Boerma et al., Surgery 215:31 (1990).
The possibility of liver transplantation has also been attempted as a potential treatment modality. This treatment, however, has generally been unsuccessful since the recurrence of cholangiocarcinomas is virtually 100%. The survivorship, therefore, appears to be no better than that of the untreated patient. See Penn et al., Surgery 110:726 (1991); Jenkins et al., Cancer Chemother. Pharmac. 23:S104 (1989). Many liver transplant centers have abandoned transplantation of patients with cholangiocarcinomas. Other centers consider transplantations for cholangiocarcinoma to be experimental in nature. In some centers, protocols employing adjuvant chemotherapy and/or radiation therapy in conjunction with transplantation are under investigation.
Non-surgical therapy of cholangiocarcinomas has been limited to patients who are found to be unresectable on the basis of either preoperative imaging or surgical exploration. Current modalities generally include variations of radiation therapy (e.g., external radiation with or without chemotherapy or the combination of external radiation or intraluminal brachytherapy). Although external irradiation with or without chemotherapy may lead to prolonged survival in some patients, the side effects of these forms of therapy are often severe as the nearby liver, gut, and spinal cord are irradiated as well. See Gunderson et al, Principles and Practice of Radiation Oncology p. 985 (1992). Palliative stenting helps to relieve the symptoms of cholangitis, but sepsis may occur in up to 88% or percutaneous stents. See Lokich et al, J. Clin Oncol. 5:969 (1987) .